Biology 478/595 – Introduction to Bioinformatics (graduate section)

The graduate section of Introduction to Bioinformatics focuses on reading original papers from the scientific literature. These papers are a mix of “classics” and more recent papers that relate to the weekly content of the lecture course. The goal of the graduate section is to gain experience in critically reading the scientific literature, and to provide survey of background literature in Computational Biology as a steppingstone to advance studies.

Course requirements

  • Each week read all papers, and be prepared to discuss them. In NIH terms this means you are a tertiary reviewer. Everyone is a tertiary reviewer of every paper.
  • Write a brief (approximately one page) report on your assigned paper focusing on:
  • very brief synopsis of paper - not a detailed description of every point; focus on the logical argument and the following questions: What data? What analysis? What is their argument and does it support their conclusions?
  • strong points of the paper
  • weak points of the paper
  • validity of conclusions

In NIH terms this is a secondary reviewer. You will be assigned one written review per week.

  • One person each week will additionally be assigned as primary reviewer. The primary reviewer, in addition to writing a review, presents a brief oral overview of the paper as an introduction to open discussion.
  • Grading is based on participation in discussion, reviews and presentations

NIH Review panels

  • NIH panels discuss proposals in a fairly narrow subject area, e.g., microbial cell biology, biological data management, cancer, etc. Usually, the proposals considered in a panel are funded by a single NIH institute.
  • Each review typically covers 50-100 proposals (3 times a year). Panelists receive proposals in advance, three reviewers are assigned to each; each reviewer generally gets 5-10 assignments.
  • Primary reviewer
  • reads the proposal in complete detail
  • Makes initial oral summary to panel
  • Write review summary to be sent to applicant
  • Secondary reviewer
  • reads proposal completely
  • provides written review (sent to applicant)
  • orally adds to primary reviewers review
  • Tertiary reviewer
  • reads proposal completely
  • provides written review
  • contributes to discussion
  • At the review meeting: 10-20 panelists : 50-100 proposals : 2-3 days
  • Before discussions, panelists provide a list of their “bottom half” of all of the proposals. A consensus from these lists are not discussed – they are “not recommended for funding”, popularly referred to being “nerfed” or “triaged”. This is what happened if you get your proposal back “unscored”. Any proposal that any panelist thinks should be discussed (as well as new investigator, post-doc and student fellowships, and a few others) are pulled back from being nerfed.
  • All panelists, whether they read the proposal or not, score on 1 (excellent) – 5 (horrible) scale. The overall score is the average over all panelists; 1.00 is perfect. By comparing scores across many panels and programs and review periods, NIH also provides a percentile ranking.

595 students
ni / Nick Ianotti /
js / JiayinShen /
aj / Alisha Johnson /
bh / BingjieHu /
mo / Mary-Jane Orr /
cp / Craig Pederson /
ty / TairanYuwen /
qw / Qiong Wu /
595 Paper schedule1⁰ = primary reviewer 2⁰ = secondary reviewer 3⁰ = tertiary reviewer
To be arranged / TBA
Week / Lecture
Topic / Assign / Papers
1 Sep - 5 Sep / Organization
8 Sep - 12 Sep / Scoring & Alignment
/ 1⁰mo
2⁰ni
3⁰all
1⁰qw
2⁰ty
3⁰all /
  • Dayhoff, MO, Schwarz, RM, Orcutt BC, A model of evolutionary change in proteins, in Atlas of Protein Sequence and Structure, Vol5, Supp. 3, 1978, MO Dayhoff, ed., National Biomedical Research Foundation, Georgetown University Medical Center, Washington DC.
  • Henikoff S, Henikoff JG., Amino acid substitution matrices from protein blocks. Proc Natl Acad Sci U S A. 1992, 89, 10915-10919.

15 Sep - 19 Sep / Alignment & Gene Finding /
  • Needleman SB, Wunsch CD., A general method applicable to the search for similarities in the amino acid sequence of two proteins., J Mol Biol. 1970 48:443-453
  • Altschul SF, Madden TL, Schaeffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ, Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, 1997, Nucleic Acids Res. 25:3389-3402.

22 Sep-25 Sep / Sequence Motifs /
  • TBA

29 Sep-3 Oct / Evolution & Phylogeny /
  • Julie D.Thompson, Desmond G.Higgins and Toby J.Gibson, CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice, Nucleic Acids Research, 1994, Vol. 22, 4673-4680,
  • David J. Lipman, Stephen F. Altschul, And John D. Kececioglu, A tool for multiple sequence alignment, Proc. Nail. Acad. Sci. USA, 86, pp. 4412-4415, 1989

6 Oct -10 Oct / Phylogenetics /
  • L. Vigilant, M. Stoneking, H. Harpending, K.
  • Hawkes, A. C. Wilson, Science 253, 1503 (1991).
  • Templeton AR, Human origins and analysis of mitochondrial DNA sequences, Science 255, 737 (1992)
  • Hedges SB, Kumar, S, Tamura K, Science 255, 737-739 (1992)
  • Ke Y, Su B, Song X, Lu D, Chen L, Li H, Qi C, Marzuki S, Deka R, Underhill P, Xiao C, Shriver M, Lell J, Wallace D, Wells RS, Seielstad M, Oefner P, Zhu D, Jin J, Huang W, Chakraborty R, Chen Z, Jin L. African origin of modern humans in East Asia: a tale of 12,000 Y chromosomes. Science 292, 1151-1153 (2001).

13 Oct - 17 Oct / Comparative Genomics /
  • R Overbeek, M Fonstein, M D’souza, G D. Pusch, and N Maltsev, The use of gene clusters to infer functional coupling, Proc. Natl. Acad. Sci. USA, 96, 2896–2901, 1999
  • Tamames, J, Evolution of gene order conservation in prokaryotes, Genome Biology 2001, 2(6):research0020.1–0020.11

20 Oct - 24 Oct / Gene expression /
  • Cluster analysis and display of genome-wide expression patterns. MB Eisen, PT Spellman, PO Brown, and D Botstein, PNAS, 95;14863-14868 (1998)
  • Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring, T. R. Golub et al., Science 286, 531-537(1999)

27 Oct - 31 Oct / Systems
Biology /
  • TBA

3 Nov - 7 Nov / Protein Families
& Evolution /
  • C Chothia and A M Lesk, The relation between the divergence of sequence and structure in proteins. EMBO J. 1986 April; 5(4): 823–826.

10 Nov - 14 Nov / HMM /
  • Gribskov, M., McLachlan, A.D., and Eisenberg, D., “Profile analysis: detection of distantly related proteins”, Proceedings of the National Academy of Sciences 84, 4355-4358, 1987.
  • Using Dirichlet mixture priors to derive hidden Markov models for protein families - M Brown, R Hughey, A Krogh, IS Mian, K Sjolander, Proceedings of the Third International Conference on Intelligent Systems for Molecular Biology, pp , 1993.

17 Nov - 21 Nov / Protein Structure /
  • Tatusov RL, KooninEV,Lipman DJ, A Genomic Perspective on Protein Families, Science 278, 631-637 (1997)

24Nov - 25 Nov / Thanksgiving holiday
1 Dec – 5 Dec / Molecular
Dynamics /
  • TBA

8 Dec - 12 Dec / Homology Modeling /
  • TBA